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Conserved domains on  [gi|971059253|ref|NP_001305267|]
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FERM domain-containing protein 4A isoform d [Homo sapiens]

Protein Classification

innate immunity activator family protein( domain architecture ID 10570578)

innate immunity activator family protein similar to Homo sapiens innate immunity activator protein that is required for optimal PRR (pattern recognition receptor)-induced signaling, cytokine secretion, and bacterial clearance

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
CUPID pfam11819
Cytohesin Ubiquitin Protein Inducing Domain; C1ORF106 also known as INAVA (Innate Immune ...
 47-182 4.17e-52

Cytohesin Ubiquitin Protein Inducing Domain; C1ORF106 also known as INAVA (Innate Immune Activator), is identified as a risk factor for the chronic inflammatory bowel diseases (IBD). Mice lacking the protein show defects in intestinal barrier integrity at steady state and greater susceptibility to mucosal infection. INAVA carries CUPID (Cytohesin Ubiquitin Protein Inducing Domain). Three other human proteins contain CUPID: FRMD4A, FRMD4B, and CCDC120- proteins implicated in neurite outgrowth, and in human cancer, Alzheimer's, celiac, and heart disease. All appear to bind the ARF-GEF (guanine nucleotide-exchange factors) cytohesin family members, such as proteins (ARF 1-4), which regulate cell membrane and F-actin dynamics. INAVA-CUPID binds cytohesin 2 (also known as ARNO), targets the molecule to lateral membranes of epithelial monolayers, and enables ARNO to affect F-actin assembly that underlies cell-cell junctions and barrier function. In the case of inflammatory signalling, ARNO can coordinate CUPID function by binding and inhibiting CUPID activity of acting as an enhancer of TRAF6 dependent polyubiquitination. In other words, ARNO acts as a negative-regulator of inflammatory responses. In summary, INAVA-CUPID exhibits dual functions, coordinated directly by ARNO, that bridge epithelial barrier function with extracellular signals and inflammation.


:

Pssm-ID: 463360  Cd Length: 136  Bit Score: 177.12  E-value: 4.17e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971059253   47 GSKGKIISGSSGSLLSSGSQESDSSQSAKKDMLAALKSRQEALEETLRQRLEELKKLCLREAELTGKLPVEYPLDPGEEP 126
Cdd:pfam11819   1 ESKGEIISSSSGSLLSSGSDSSTSSEKQKKEKTAALKKKQQALQERLELKLEELKKLCLREAELTGKLPKEYPLEPGEKP 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 971059253  127 PIVRRRIGTAFKLDEQKILPKGEEAELERLEREFAIQSQITEAARRLASDPNVSKK 182
Cdd:pfam11819  81 PQVRRRVGTAFKLDEQHVLQYAEDPELESLEREFALQQQIVEAARRLALEPNLSKT 136
PH-like super family cl17171
Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ...
 1-18 1.88e-05

Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.


The actual alignment was detected with superfamily member cd13191:

Pssm-ID: 473070  Cd Length: 113  Bit Score: 44.26  E-value: 1.88e-05
                         10
                 ....*....|....*...
gi 971059253   1 MAISQHQFYLDRKQSKSK 18
Cdd:cd13191   96 MAIAQHQFYLDRKQSKKK 113
 
Name Accession Description Interval E-value
CUPID pfam11819
Cytohesin Ubiquitin Protein Inducing Domain; C1ORF106 also known as INAVA (Innate Immune ...
 47-182 4.17e-52

Cytohesin Ubiquitin Protein Inducing Domain; C1ORF106 also known as INAVA (Innate Immune Activator), is identified as a risk factor for the chronic inflammatory bowel diseases (IBD). Mice lacking the protein show defects in intestinal barrier integrity at steady state and greater susceptibility to mucosal infection. INAVA carries CUPID (Cytohesin Ubiquitin Protein Inducing Domain). Three other human proteins contain CUPID: FRMD4A, FRMD4B, and CCDC120- proteins implicated in neurite outgrowth, and in human cancer, Alzheimer's, celiac, and heart disease. All appear to bind the ARF-GEF (guanine nucleotide-exchange factors) cytohesin family members, such as proteins (ARF 1-4), which regulate cell membrane and F-actin dynamics. INAVA-CUPID binds cytohesin 2 (also known as ARNO), targets the molecule to lateral membranes of epithelial monolayers, and enables ARNO to affect F-actin assembly that underlies cell-cell junctions and barrier function. In the case of inflammatory signalling, ARNO can coordinate CUPID function by binding and inhibiting CUPID activity of acting as an enhancer of TRAF6 dependent polyubiquitination. In other words, ARNO acts as a negative-regulator of inflammatory responses. In summary, INAVA-CUPID exhibits dual functions, coordinated directly by ARNO, that bridge epithelial barrier function with extracellular signals and inflammation.


Pssm-ID: 463360  Cd Length: 136  Bit Score: 177.12  E-value: 4.17e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971059253   47 GSKGKIISGSSGSLLSSGSQESDSSQSAKKDMLAALKSRQEALEETLRQRLEELKKLCLREAELTGKLPVEYPLDPGEEP 126
Cdd:pfam11819   1 ESKGEIISSSSGSLLSSGSDSSTSSEKQKKEKTAALKKKQQALQERLELKLEELKKLCLREAELTGKLPKEYPLEPGEKP 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 971059253  127 PIVRRRIGTAFKLDEQKILPKGEEAELERLEREFAIQSQITEAARRLASDPNVSKK 182
Cdd:pfam11819  81 PQVRRRVGTAFKLDEQHVLQYAEDPELESLEREFALQQQIVEAARRLALEPNLSKT 136
FERM_C_FRMD4A_FRMD4B cd13191
FERM domain C-lobe of FERM domain-containing protein 4A and 4B (FRMD4A and 4B); FRMD4A is part ...
 1-18 1.88e-05

FERM domain C-lobe of FERM domain-containing protein 4A and 4B (FRMD4A and 4B); FRMD4A is part of the Par-3/FRMD4A/cytohesin-1 complex that activates Arf6, a central player in actin cytoskeleton dynamics and membrane trafficking, during junctional remodeling and epithelial polarization. The Par-3/Par-6/aPKC/Cdc42 complex regulates the conversion of primordial adherens junctions (AJs) into belt-like AJs and the formation of linear actin cables. When primordial AJs are formed, Par-3 recruits scaffolding protein FRMD4A which connects Par-3 and the Arf6 guanine-nucleotide exchange factor (GEF), cytohesin-1. FRMD4B (also called GRP1-binding protein, GRSP1) is a novel member of GRP1 signaling complexes that are recruited to plasma membrane ruffles in response to insulin receptor signaling. The GRSP1/FRMD4B protein contains a FERM protein domain as well as two coiled coil domains and may function as a scaffolding protein. GRP1 and GRSP1 interact through the coiled coil domains in the two proteins. The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs) , the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.


Pssm-ID: 270012  Cd Length: 113  Bit Score: 44.26  E-value: 1.88e-05
                         10
                 ....*....|....*...
gi 971059253   1 MAISQHQFYLDRKQSKSK 18
Cdd:cd13191   96 MAIAQHQFYLDRKQSKKK 113
 
Name Accession Description Interval E-value
CUPID pfam11819
Cytohesin Ubiquitin Protein Inducing Domain; C1ORF106 also known as INAVA (Innate Immune ...
 47-182 4.17e-52

Cytohesin Ubiquitin Protein Inducing Domain; C1ORF106 also known as INAVA (Innate Immune Activator), is identified as a risk factor for the chronic inflammatory bowel diseases (IBD). Mice lacking the protein show defects in intestinal barrier integrity at steady state and greater susceptibility to mucosal infection. INAVA carries CUPID (Cytohesin Ubiquitin Protein Inducing Domain). Three other human proteins contain CUPID: FRMD4A, FRMD4B, and CCDC120- proteins implicated in neurite outgrowth, and in human cancer, Alzheimer's, celiac, and heart disease. All appear to bind the ARF-GEF (guanine nucleotide-exchange factors) cytohesin family members, such as proteins (ARF 1-4), which regulate cell membrane and F-actin dynamics. INAVA-CUPID binds cytohesin 2 (also known as ARNO), targets the molecule to lateral membranes of epithelial monolayers, and enables ARNO to affect F-actin assembly that underlies cell-cell junctions and barrier function. In the case of inflammatory signalling, ARNO can coordinate CUPID function by binding and inhibiting CUPID activity of acting as an enhancer of TRAF6 dependent polyubiquitination. In other words, ARNO acts as a negative-regulator of inflammatory responses. In summary, INAVA-CUPID exhibits dual functions, coordinated directly by ARNO, that bridge epithelial barrier function with extracellular signals and inflammation.


Pssm-ID: 463360  Cd Length: 136  Bit Score: 177.12  E-value: 4.17e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971059253   47 GSKGKIISGSSGSLLSSGSQESDSSQSAKKDMLAALKSRQEALEETLRQRLEELKKLCLREAELTGKLPVEYPLDPGEEP 126
Cdd:pfam11819   1 ESKGEIISSSSGSLLSSGSDSSTSSEKQKKEKTAALKKKQQALQERLELKLEELKKLCLREAELTGKLPKEYPLEPGEKP 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 971059253  127 PIVRRRIGTAFKLDEQKILPKGEEAELERLEREFAIQSQITEAARRLASDPNVSKK 182
Cdd:pfam11819  81 PQVRRRVGTAFKLDEQHVLQYAEDPELESLEREFALQQQIVEAARRLALEPNLSKT 136
FERM_C_FRMD4A_FRMD4B cd13191
FERM domain C-lobe of FERM domain-containing protein 4A and 4B (FRMD4A and 4B); FRMD4A is part ...
 1-18 1.88e-05

FERM domain C-lobe of FERM domain-containing protein 4A and 4B (FRMD4A and 4B); FRMD4A is part of the Par-3/FRMD4A/cytohesin-1 complex that activates Arf6, a central player in actin cytoskeleton dynamics and membrane trafficking, during junctional remodeling and epithelial polarization. The Par-3/Par-6/aPKC/Cdc42 complex regulates the conversion of primordial adherens junctions (AJs) into belt-like AJs and the formation of linear actin cables. When primordial AJs are formed, Par-3 recruits scaffolding protein FRMD4A which connects Par-3 and the Arf6 guanine-nucleotide exchange factor (GEF), cytohesin-1. FRMD4B (also called GRP1-binding protein, GRSP1) is a novel member of GRP1 signaling complexes that are recruited to plasma membrane ruffles in response to insulin receptor signaling. The GRSP1/FRMD4B protein contains a FERM protein domain as well as two coiled coil domains and may function as a scaffolding protein. GRP1 and GRSP1 interact through the coiled coil domains in the two proteins. The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs) , the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.


Pssm-ID: 270012  Cd Length: 113  Bit Score: 44.26  E-value: 1.88e-05
                         10
                 ....*....|....*...
gi 971059253   1 MAISQHQFYLDRKQSKSK 18
Cdd:cd13191   96 MAIAQHQFYLDRKQSKKK 113
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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